MDA awarded a research grant totaling $398,532 over three years to Michio Hirano, professor of neurology and chief of the neuromuscular division at Columbia University Medical Center in New York. The funds will help support Hirano’s study of “molecular bypass therapy” for a mitochondrial myopathy called thymidine kinase 2 (TK2) deficiency.

Cellular “energy factories” called mitochondria generate the energy that fuels cells. Defects in mitochondria, which have their own DNA, are the causes of numerous human diseases that typically affect muscle and the brain.

One such disease, TK2 deficiency, usually begins in infancy. The disease also can manifest as adult-onset eye and limb muscle weakness. An enzyme (type of protein) called TK2 is required to synthesize the molecular building blocks of mitochondrial DNA.

With a previous MDA grant, Hirano and colleagues generated a research mouse model that has severely decreased TK2 activity and that develops muscle weakness similar to that of people with the infantile-onset form of TK2 deficiency.

In preliminary studies, administration of compounds to bypass the defective TK2 enzyme slowed the progression of the disease and doubled the life spans of the mice. Now, Hirano’s team is working to optimize the molecular bypass treatment in the TK2 mice.

Intensive research has revealed more than 200 genetically distinct mitochondrial diseases as well as novel therapeutic approaches for them, Hirano says. If successful, his new work could lead to the development of therapies for human TK2 deficiency and related diseases.

Funding for this MDA grant began Aug. 1, 2012.